Benign glandular cells in posthysterectomy vaginal smears: the incidence is higher than expected

In this study, we have investigated the frequency and clinical significance of glandular cells in posthysterectomy vaginal smears. The slides of vaginal cuff smears of 290 patients were reviewed. The glandular cells were categorized into three groups: (1) squamous metaplastic-like cells; (2) columnar endocervical-like cells; and (3) small round cuboidal cells. Glandular cells were found in 39 (13%) of the 290 vaginal smears. Group 1 type cells were seen in 76% (n = 30), group 2 type cells in 38% (n = 15) and group 3 type cells in 47% (n = 19) of the smears. In 19 (48%) of the smears combination of two or three groups were seen. The presence of glandular cells showed a strong association with inflammation/repair as a background finding in the smears. No correlation could be found between the presence of atrophy and history of chemotherapy or radiotherapy. Apart from these there was a prominent increase in reporting benign glandular cells after the application of the current Bethesda 2001 reporting criteria in our laboratory. As a result our study showed that the finding of glandular cells in posthysterectomy vaginal smears is more frequent than expected and most of them could be related to inflammatory and regenerative processes in the absence of a clearly identified underlying cause.     

Intraobserver and interobserver variability in the quality assessment of cervical smears

Intraobserver and interobserver variability in assessing the quality of cervical smears, as measured by the presence or absence of endocervical columnar cells and squamous metaplastic cells, was evaluated. In total, 180 cervical smears representing the most important cytologic diagnoses were anonymously rescreened twice by 19 observers with an interval of six months. An absence of endocervical columnar cells was proven to correlate with a high percentage of false-negative diagnoses. Intraobserver agreement on the presence or absence of endocervical columnar cells was 85.7% between the two screenings. A predictive value of 57.7% was found for a negative scoring (absence of these cells) while the predictive value of a positive scoring (presence of endocervical cells) was 87.3%. Of the observer scorings, 83.9% concurred with the final diagnosis; there was no significant correlation between that concurrence and the number of years of experience in cytopathology of the observer. For squamous and squamous metaplastic cells in the cervical smear the predictive value of a negative scoring (absence) was only 20.6%. Compared to the final diagnosis, 69.5% of these scorings matched. A significant and relatively high correlation with the experience of the observer was found for the scoring for the presence of metaplastic cells. Even though the predictive values of these quality scorings were relatively low a significantly higher risk for false diagnoses was established when negative scorings were given. It is therefore advisable to have smears with negative scorings for endocervical columnar cells and squamous metaplastic cells always rescreened by another observer.     

Relationship between the diagnosis of epithelial abnormalities and the composition of cervical smears

The significance of endocervical columnar cells as a high-quality parameter of cervical smears was studied. In a cohort of women with two successive screenings, the consistency of the cellular composition of the cervical smears and the relation between the cellular composition of the smears and the frequency of the diagnosis of abnormal epithelial changes was investigated. At the first screening, a significantly higher number of epithelial abnormalities was found in smears with endocervical columnar cells than in smears without endocervical columnar cells. A significantly higher number of abnormal epithelial changes was found on the second screening in smears from women whose smears from the first screening did not contain endocervical columnar cells than in smears from women whose smears from the first screening did contain endocervical columnar cells. The presence of endocervical cells should be considered a very important indicator of the quality of cervical smears. The chance of missing an abnormal epithelial change is increased in smears without endocervical columnar cells. When endocervical columnar cells are absent, the smear should be considered to be of unreliable quality and a repeat smear should be taken after a short interval, unless the absence of columnar cells can be satisfactorily explained.     

Anal cytology in an HIV-positive population: a retrospective analysis

OBJECTIVE: To retrospectively evaluate cellularity and correlate the presence of columnar cells with specimen interpretation in conventionally prepared anal cytologic smears from an HIV-positive population. STUDY DESIGN: Two cytopathologists and 1 senior cytotechnologist, blinded to the original diagnosis, screened 114 samples from 110 patients collected between 1997 and 2002. One hundred nine males and 1 female were included, age ranging from 23 to 52 years. Discrepancies were reviewed for consensus. The interpretations, cellularity, and presence or absence of columnar cells were noted. The relationships between diagnosis and presence of columnar cells, visible anal lesions, concurrent HIV viral load and CD4+ T-cell counts were assessed. RESULTS: The cytologic findings were as follows: 7, unsatisfactory (6%); 29, negative (25%); 25, atypical squamous cells of undetermined significance (22%); and 53, dysplasia (47%) (42 anal intraepithelial lesion 1 [37%] and 11 anal intraepithelial lesion 2/3 [10%]). Nearly 50% of the smears, 51, showed the presence of columnar cells (45%); 37 of those specimens had some degree of dysplasia (74%). Of the 63 specimens with no columnar cells, 16 (25%) showed dysplasia. Columnar cells were absent from all unsatisfactory specimens. CONCLUSION: A highly significant association between the presence of columnar cells and anal intraepithelial lesion (p<0.001) and a significant association between the presence of columnar cells and atypical cytology when a visible lesion was absent (p=0.0019) were found. No significant relationship was found between the presence/degree of dysplasia and CD4+ T-cell counts or HIV viral load. Lack of clinical follow-up precluded evaluation of the false negative rates in this data set.     

Influence of endocervical status on the cytologic prediction of cervical intraepithelial neoplasia.

A case-control analysis of the endocervical status of smears that preceded a histologic diagnosis of cervical intraepithelial neoplasia (CIN) showed that smears which correctly predicted CIN were significantly more likely to include metaplastic cells than were smears reported to be negative. There was no significant difference between the smears with respect to the presence of columnar cells. A high level of agreement was apparent between scientists in determining both columnar and metaplastic cell status. A discussion of the definition, role and potential impact of endocervical status in the prevention of cervical cancer is presented.     

Goblet-like cells in atrophic vaginal smears and their histologic correlation. Possible confusion with endocervical cells.

The occurrence and origin of goblet-like cells seen between clusters of parabasal cells in atrophic vaginal smears were investigated. The goblet-like cells were cytologically identified in the vaginal smears from 23 (19.2%) of 120 patients whose smears showed an atrophic pattern, but without any inflammatory, dysplastic or malignant changes. Histologically, these cells were found in sections from 6 (18.8%) of 32 elderly women with atrophic vaginal epithelium. The goblet-like cells were situated among the squamous cells of the upper layer of the atrophic squamous epithelium from the vagina to the portio. These goblet-like cells in atrophic smears were initially misinterpreted as endocervical cells, which are regarded as a marker of smear adequacy in the cytologic screening for cancer of the uterine cervix. The correct interpretation of these goblet-like cells in smears from postmenopausal and elderly women is thus obviously important in assessing the adequacy of the sample for the detection of abnormal cells.     

Postoperative changes in vaginal smears after vaginal reconstruction with a free skin graft

Surgical vaginal reconstruction was performed by a free skin graft in two patients without a vagina. The postoperative changes in vaginal smears collected from the artificial vaginas were observed for about two years. Marked operation-induced inflammatory changes were observed until the second postoperative month. After the third postoperative month, the background became relatively clear. Cyanophilic and eosinophilic superficial cells, intermediate cells and D?derlein bacilli were observed occasionally in addition to keratotic cells. Six to 12 months after surgery, the vaginal smears showed little abnormality, except for the presence of keratotic cells. The changes in the vaginal smears after the third month show that the artificial vaginal epithelium changed cytologically to an almost normal vaginal mucosa that, although not histologically complete, responded to hormones. The presence of D?derlein bacilli suggests that the regional environment of the artificial vagina was almost the same as that of the normal vagina.     

Cellular Differences Between True Negative and False Negative Papanicolaou Smears

A matched case-control study of 123 false negative Papanicolaou smears and 488 true negative Papanicolaou smears was undertaken to determine the association between the types of cells present on the smear and the correctness of the cytology report. the false negative slides were significantly more likely to include endocervical columnar cells than the true negative slides (odds ratio 1.90, 95% confidence interval (CI) 1.21–3.01). No statistically significant difference in metaplastic cell status was evident (odds ratio 1.48, 95% CI 0.95–2.30). When considered together, metaplastic and/or columnar cells were significantly more likely to be present in false negative smears than in true negative smears (odds ratio 1.87, 95% CI 1.13–3.08). the implications of these findings for improving the accuracy of cervical cytology for the detection of precancerous lesions are discussed.     

New observations on the significance of nipplelike protrusions in the nuclei of endocervical cells

Nuclear nippling was noted in the endocervical columnar cells in smears taken from women of child-bearing age who were using a progesterone-only contraceptive. The phenomenon occurred most consistently in smears from women who were amenorrheic, a condition indicative of a marked decrease of estrogen activity. These observations do not support the previous explanations linking nuclear nippling to estrogenic stimulation. Close observation of the progress of these nuclear protrusions showed that they represented an arrested attempt at nuclear division, with the inhibition possibly due to the rapid rise of the progestogen level, which may be caused either by the use of progesterone-only contraceptives or by the onset of ovulation. The presence of nuclear nippling in normal smears may thus establish the occurrence of ovulation; its observation in metastatic tumors should indicate that the primary tumor has a columnar cell component.     

The cytology of vaginal, cervical and endometrial smears obtained at the time of embryo transfer during in vitro fertilization

Seventy-four women enrolled in an in vitro fertilization (IVF) program had cytologic smears of the vagina, cervix and endometrium obtained at the time of embryo transfer (ET). Of these, 68 vaginal, 46 cervical and 25 endometrial smears were available for cytologic examination. Of the 68 vaginal smears, 4% showed a proliferative pattern, 40% were early secretory and 56% were advanced secretory. The 46 cervical smears demonstrated a delayed hormonal effect, with 70% showing a proliferative pattern, 23% early secretory and 7% advanced secretory cytology. Endometrial cells were obtained only when the Jones catheter, which has a side opening, was used. Twenty-two patients had both vaginal smears and suitable endometrial smears. Of these, 8 of the 9 patients with early secretory vaginal cytology had secretory endometrium while 10 of the 12 patients with mid-secretory vaginal cytology had secretory endometrium. The value of endometrial cytology in predicting conception following IVF-ET is unknown. It seems, however, that a good correlation exists between endometrial and vaginal cytology and that the latter may be of value as an additional, noninvasive tool for the evaluation of endometrial development.     

Detecting ovulation in Macaca nemestrina by correlation of vaginal cytology, body temperature and perineal tumescence with laparoscopy

Vaginal cytology, basal body temperature, and perineal tumescence were correlated with laparoscopic observations during the menstrual cycles of five pigtail monkeys (Macaca nemestrina) of known fertility. Percentages of cells obtained in vaginal smears revealed systematic variation in the presence of cell types in relation to the menstrual cycle. Measuring the percentage of exfoliate vaginal epithelial cells containing pyknotic nuclei proved to be of little value for separating the menstrual cycle into its follicular and luteal phases, nor did body temperature provide an accurate index for the occurrence of ovulation. Perineal tumescence, however, measured from the first day of menses to onset of detumescence, was a reliable indicator of the lengths of the follicular and luteal phases as correlated with laparoscopic confirmation of ovulation. Maximal perineal tumescence usually occurred within 12 hours of ovulation, although on one occasion the two events were separated by 48 hours.     

Papanicolaou smears without endocervical cells. Are they inadequate?

The retrieval of columnar endocervical cells from the squamocolumnar junction has generally been considered to be a measure of the adequacy of a Papanicolaou smear; this implies that, if endocervical cells are absent from the smear, the examination for cervical cancer is less than optimal and should be repeated. A study was undertaken to determine if women with serial Papanicolaou smears without endocervical cells showed an increased rate of development of cervical atypia in subsequent smears. The smears of 18,914 women were evaluated for the presence or absence of endocervical cells and for the subsequent development of an abnormal smear over a four-year study period. No differences were found in the rates of atypia between women with and those without endocervical cells on serial Papanicolaou smears. Women with prior Papanicolaou smears without endocervical cells were much more likely to have a subsequent Papanicolaou smear without endocervical cells. Although no difference was found in the incidence of cervical atypia in the two groups during this short study period, these results should be considered to be preliminary.     

Relationships between ovarian morphology, vaginal cytology, serum progesterone, and urinary immunoreactive pregnanediol during the menstrual cycle of the cynomolgus monkey

Three different indices of ovulation and luteal activity were studied in eight regularly cycling cynomolgus monkeys. A significant relation between changes in serum progesterone and immunoreactive pregnanediol (I-PD) in urine was obtained. The occurrence of ovulation could be determined reliably from a change in the ratio of cornified to basal epithelial cells in vaginal smears, and luteal activity could be assessed reliably from daily measurements of urinary pregnanediol. The time of ovulation could be defined more precisely by daily I-PD radioimmunoassays than by the vaginal smear pattern. Measurements of I-PD also have the advantage of ease and noninvasiveness over serum progesterone determinations. More detailed information about changes in hormonal activities could not be obtained reproducibly from thorough examination of cell types in vaginal smears.     

The influence of sample takers on the cellular composition of cervical smears

In a population-based cervical cancer screening program, the performances of five sample takers and their influence on the cellular composition of the smears and the numbers of epithelial abnormalities diagnosed were analyzed. As measured by the presence of endocervical columnar cells, there were remarkable variations in the quality of the smears between sample takers and between years of sampling. There was also a positive relationship between the presence of endocervical columnar cells in the smear and the number of epithelial abnormalities found. A lower quality of smear was reflected by a lower incidence of epithelial atypical changes found, both between sample takers and by a single sample taker over a period of time. These findings show that sample takers influence the cellular composition of smears and, therefore, the diagnostic outcome of smear screening. Their competence in executing their tasks must be frequently reviewed.     

Relationship between the morphology of Candida cells and vaginal discharge

The aim of this study was to detect whether there is a correlation between the dimorphic pattern of Candida cells and various types of vaginal discharge. For this purpose, 2861 Papanicolaoustained cervicovaginal smears were examined cytologically and 265 of 2861 (9.26%) were diagnosed as having Candida cells. The 88 of 295 (29.83%) were identified as having blastospores only, 135 of 295 (45.76%) as having "hyphae only", and 47 of 295 (15.93%) as having both blastospores and hyphae of candida cells. There was a significant correlation between the type of candida cells and vaginal discharge (p < 0.05). The white-cheesy type vaginal discharge was the most prominent symptom for the observation the "hyphae only" following "blastospores only" and both blastospores and hyphae of Candida cells. It was suggested that hyphael form of Candida cells is the most pathogenic pattern and white-cheesy vaginal discharge is a marker for the presence of hyphael form in the vaginal mucosa.     

Cellular composition of cervical smears in relation to the day of the menstrual cycle and the method of contraception

The influence of the day of the menstrual cycle and the method of contraception on the cellular composition of cervical smears was investigated. The percentage of unsatisfactory smears during the first four days of the cycle was understandably very high, leaving only 80% of the smears of sufficient quality for cytologic diagnosis. The percentage of smears of insufficient quality during the remainder of the cycle was significantly higher in women using oral hormonal contraceptives. The percentages of smears containing endocervical columnar cells, a criterion for judging smears to be of high quality, differed significantly among women using different modes of contraception. The highest percentage of smears without endocervical columnar cells was found in women using oral contraceptives; during the first half of the cycle in these women, smears were of higher quality than during the second half of the cycle. In women not practicing contraception or using nonhormonal methods of contraception, the differences in cellular composition during the cycle, though significant, were too small to be of practical importance. Women using oral contraceptives thus have an increased risk for a potential false-negative diagnosis because of the higher percentage of smears of unreliable quality taken in these women. In women using oral hormonal contraceptives, smears should be taken during the first half of the cycle because of the higher percentage of smears of high quality in that period.     

Cytodiagnosis of endometrial malignant mixed mesodermal tumor

The accuracy of endometrial aspiration smears obtained with the Isaacs cell sampler in the diagnosis of malignant mixed mesodermal tumors (MMMT) was compared to the results obtained with routine cervical and vaginal smears in five cases of MMMT found in a series of 220 endometrial aspirations. Cervical and vaginal smears previously taken on these patients were positive for adenocarcinoma or MMMT in two cases and suspicious for adenocarcinoma in the remaining three cases. Endometrial aspirates were positive for MMMT in three cases and positive for adenocarcinoma or MMMT in two cases. The endometrial aspiration smears contained a variety of cells: malignant glandular, squamous, spindly stromal, undifferentiated, osteoid and tumor giant cells; chondrocytes and free psammoma bodies were also observed. These cases indicated that endometrial aspiration can accurately detect the heterologous cellular elements found in MMMT and is an effective technique in its diagnosis.     

The use of cytological examination of vaginal smears (CEVS) in the selection of rabbits for superovulation

In the present study, we examined two factors associated with the reproduction of rabbit does, cytology of vaginal smears and color of vulva, as potential predictors of the success of superovulation treatment. Vulval color and vaginal smear cytology were assessed in 55 young New Zealand does. Superovulation was then induced by a single administration of eCG (20 IU/kg BW i.m.). Does were artificially inseminated 3 days later, followed by intravenous administration of hCG (120 IU per animal). Does were classified with regard to vulval color (white, rose, red, purple), and the predominant cell type in the vaginal smear (i.e. parabasal, intermediate, superficial, or anuclear). Furthermore, we categorized cells into two groups because we usually observed parabasal and intermediate cells (Group A), and superficial and anuclear cell (Group B) in the same smear. Does were humanely killed 19 h after administration of hCG and the total numbers of corpora lutea (CLs), oocytes, and zygotes (i.e. 1-cell embryos) were determined. The zygotes were assessed by morphological appearance and classified as normal or abnormal. The color of the vulva at the time of eCG treatment did not predict the success of superovulation in terms of the number of CLs, oocytes or zygotes. Does with predominantly superficial cells in vaginal smears yielded significantly fewer CLs and oocytes-zygotes (OZ) compared to does with predominantly parabasal, intermediate, or anuclear cells (P<0.05). Does with predominantly superficial cells in vaginal smears tended to yield fewer normal zygotes (nZ), but this reached significance only when compared to does with predominantly parabasal cells (P<0.05). Does in Group A yielded significantly more (P<0.05) CLs, OZ and nZ compared to does in Group B. Does with predominantly parabasal and intermediate cells in vaginal smears and rose color vulva tended to yield more OZ and nZ (P<0.05). These results suggest that the cytology of vaginal smears may help identify does with a significantly higher likelihood of yielding low numbers of CLs, oocytes, or nZ.     

The significance of endocervical cells in the diagnosis of cervical epithelial changes

A study was made of the relationship of endocervical columnar cells to the cytologic identification of abnormality in the cervix. From a population of women participating in a cervical cancer screening program, a group of women was selected whose smears theoretically should have contained endocervical columnar cells. Endocervical cells were present in 93.1% of the smears and absent in 6.9%. A significantly higher number of moderately and severely atypical epithelial changes was found in smears with endocervical cells as compared with smears without endocervical cells.     

Cytomorphology of hyaline-vascular Castleman''s disease: a diagnostic challenge

OBJECTIVE: Hyaline-vascular Castleman's disease (CD) is difficult to diagnose on fine needle aspiration and may be mistaken to be a lymphoreticular malignancy because of the presence of large cells having nuclei showing atypical features. The cytomorphological findings in three histopathologically documented cases of hyaline-vascular CD were evaluated to a set of cytomorphological criteria which could help in the identification of this condition on aspirate smears. METHODS: The Papanicolaou and Diff-Quik stained smears from three cases of histologically documented hyaline-vascular CD were reviewed by one author. After review the following cytomorphological criteria were suggested to be indicators of the lesion. (i) The presence of large oval to round cells having ill-defined cytoplasmic margins and large nuclei with irregular nuclear outlines having fine or coarse chromatin giving a crumpled tissue paper appearance. (ii) A polymorphous population of lymphoid cells predominantly of small lymphocytes in the background. The smears from these three cases were then mixed with smears from four cases of reactive lymphoid hyperplasia and three cases of Hodgkin's lymphoma. These ten cases were blindly evaluated by two other cytopathologists in order to evaluate the utility of the proposed criteria in identifying CD. RESULTS: The cytomorphological criteria seen in the methodology section were present in all the cases. These features were helpful in distinguishing CD from reactive lymphoid hyperplasias and Hodgkin's Lymphomas in all cases except one case. CONCLUSION: Although hyaline-vascular CD is a difficult diagnostic entity on aspirate material the presence of large histiocytic cells with a crumpled tissue paper appearance of the nuclei in a background of small lymphocytes are useful indicators for suspecting this lesion. However, these findings should be analysed in larger studies to determine if they could in anyway reduce the diagnostic dilemma in cases of CD.